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ClinicalDIGEST 2
Diabetes and the
risk of cancer is
currently a hot
topic. Four articles (Colhoun
et al; Currie et al; Hemkens
et al; Jonasson et al) published
in the September 2009 issue of
Diabetologiasought to explore
whether treatment with the
long-acting insulin analogue insulin glargine could
possibly be associated with an increased risk of
cancer. These articles gave conflicting results,
and the methodological quality of some of them
has been debated. No alteration in prescribing
was suggested following these publications, but
further research was recommended. Further
studies should be published later this year.
It is emerging that diabetes itself is associated
with an increased risk of certain forms of
cancer. Obesity is associated with an increased
risk of cancer, and diabetes is associated with
obesity. This could explain, at least partially, the
association between cancer and diabetes.Another way that cancer could be associated
with diabetes is through hyperglycaemia. In
the article by Johnson and Bowker (2011;
summarised alongside), they seek to examine
this possibility. The authors conducted a
meta-analysis of four trials reporting cancer
mortality rates for an intensively controlled
versus a standard controlled glycaemic
group. In these studies, 222 cancer deaths
were experienced in 53 892 person-years of
intensified glycaemic control compared with
155 cancer deaths during 38 743 person-years
of standard control.
In a further three studies, cancer incidence
was reported: 357 events in 47974 person-
years with improved glycaemic control and
380 events in 45009 person-years in the
control arm. The authors conclude that data from
large, randomised, controlled trials of intensified
glycaemic control suggest that cancer risk is not
reduced by improving glycaemic control in people
with type 2 diabetes. Therefore, this article does
not support the hypothesis that hyperglycaemia is
causally linked to increased cancer risk.
Colhoun HM; SDRN Epidemiology Group (2009) Use of Insulinglargine and cancer incidence in Scotland: a study from theScottish Diabetes Research Network Epidemiology Group.Diabetologia52: 175565
Currie CJ, Poole CD, Gale EA (2009) The influence of glucose
lowering therapies on cancer risk in type 2 diabetes. Diabetologia52: 176677
Hemkens LG, Grouven U, Bender R et al (2009) Risk ofmalignancies in patients with diabetes treated with human insulinor insulin analogues a cohort study. Diabetologia52: 173244
Jonasson JM, Ljung R, Talback M et al (2009) Insulin glargineand short term incidence of malignancies a population basedfollow up study in Sweden. Diabetologia52:174554
Roger Gadsby, GPand Senior Lecturer,Centre for PrimaryHealthcare Studies,Warwick University,Coventry
Is cancer risk associated with glycaemic control?
82 Diabetes Digest Volume 10 Number 2 2011
Safety and efficacyof linagliptin in
people with T2D
1In this study, the safety and
efficacy of linagliptin (a dipeptidyl
peptidase-4 inhibitor) as add-on
therapy to metformin was assessed in
poorly controlled people with T2D.
2Participants (aged 1880 years)continued on metformin and
were randomised to receive linagliptin
5 mg/day (n=524) or placebo
(n=177) for 24 weeks.
3Baseline mean HbA
1clevels
were 8.0% (64 mmol/mol) and
8.1% (65 mmol/mol) in the placebo
and treatment groups, respectively;
these levels were changed by0.15% (1.6 mmol/mol) and 0.49%
(5.4 mmol/mol) at study end.
4Neither group was associated
with significant changes in mean
body weight (placebo, 0.5 kg;
linagliptin, 0.4 kg) and occurrences
of hypoglycaemia were rare (2.8% and
0.6%, respectively).
5The authors concluded that linagliptin
add-on therapy in people with T2D
showed improved glycaemic control
compared with placebo.
Taskinen MR, Rosenstock J, Tamminen I et al(2011) Safety and efficacy of linagliptin as add-on therapy to metformin in patients with type 2diabetes: a randomized, double-blind, placebo-controlled study. Diabetes Obes Metab13: 6574
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Intensive glycaemic
control does not
reduce cancer risk
1The aim of this study was to
determine whether data from
major randomised controlled trials
would support the hypothesis that
improving glycaemic control wouldreduce the risk of cancer or cancer
mortality in T2D.
2The authors assessed data from
the UKPDS (UK Prospective
Diabetes Study) 33, UKPDS 34,
ACCORD (Action to Control
Cardiovascular Risk in Diabetes),
VADT (Veterans Affairs Diabetes
Trial), ADVANCE (Action in Diabetes
and Vascular Disease: Preterax and
Diamicron MR Controlled Evaluation),
PROactive (Prospective PioglitazoneClinical Trial in Macrovascular Events)
and RECORD (Rosiglitazone Evaluated
for Cardiac Outcomes and Regulation of
Glycaemia in Diabetes) trials.
3The UKPDS 33, UKPDS 34,
ACCORD and VADT studies
reported cancer mortality rates of
222 events in 53892 person-years
with intensive control and 155 events
in 38743 person-years with standard
control; the overall pooled risk ratio (RR)
for cancer mortality was 1.00 (P=0.98).
4The ADVANCE, PROactive
and RECORD studies reported
cancer incidence of 357 events in
47 974 person-years with improved
glycaemic control and 380 events in
45 009 person-years in the control
arms; the pooled RR for cancer
incidence was 0.91 (P=0.20).
5No evidence was found to support
the hypothesis that hyperglycaemia
is a modifiable risk factor for increased
incidence of cancer or cancer mortality
in T2D.
Johnson JA, Bowker SL (2011) Intensiveglycaemic control and cancer risk intype 2 diabetes: a meta-analysis of major trials.Diabetologia54: 2531
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DIABETOLOGIA
DIABETES, OBESITY& METABOLISM
Management & prevention of type 2 diabetes
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ClinicalDIGESTType 2 diabetes
84 Diabetes Digest Volume 10 Number 2 2011
Improved glycaemic
control with
saxagliptin treatment
1This multicentre, randomised,
placebo-controlled study assessed
the safety and efficacy of saxagliptin in
people with T2D and renal impairment.
2Adults with inadequately controlled
diabetes (HbA1clevel 711%;
5397 mmol/mol) and renal impairment
(creatinine clearance [CrCl] rate of